Over 30,000 Americans die each year from prostate cancer, making it the second most lethal form of cancer affecting men in the U.S. Many of these deaths could be prevented if the cancers were detected before the tumor escaped the prostate. Our goal for this research project is to develop a simple blood test that will dramatically improve a physician's ability to judge whether an abnormal PSA level is due to a metastatic prostate tumor or to a benign prostatic condition. The availability of this assay will eliminate thousands of unnecessary prostate biopsies with their inherent pain, undesirable side effects, and cost. In addition, the Vivo assay should make it possible to detect a large portion of the 15-20% of existing prostate tumors that are missed by the PSA test. Vivo's research plan is designed to identify tumor-associated autoantibodies which may be present at low levels in normal serum but increase during the early stages of prostate cancer. Our approach is particularly novel in that it focuses on autoantibodies of the IgM and IgA isotypes which are generally ignored in traditional epitope discovery strategies. Our approach also bypasses the common practice of pre-subtracting the phage library against Igs from normal sera;while the subtractive step may speed up the overall biopanning process, it also interferes with the discovery of potentially important diagnostic antibodies which are already present at low levels in normal sera but are elevated as the cancer progresses. We propose to achieve two specific aims: 1. To identify a group of peptides that are recognized by either IgM or IgA autoantibodies in sera from patients with aggressive prostate cancer;and 2. To compare the reactivities of these peptides with individual patient sera (aggressive and indolent cancers;BPH) and with healthy controls. To achieve these goals, we will prepare several thousand individually-amplified peptide phage clones and will use high throughput techniques to measure their reactivities with multiple serum samples. The new assay will provide significant improvements in the specificity and sensitivity of prostate cancer diagnostics, and this should lead to wider acceptance of screening programs for the early detection of prostate cancer and to significant declines in the prostate cancer death rate. PUBLIC HEALTH RELEVANCE: The goal of this research project is to develop a new blood test for the early diagnosis of prostate cancer which will make the current PSA test more sensitive and more reliable. This will encourage more physicians to support annual screening of their patients at risk for this cancer and will thus lead to decreases in the death rate due to this disease.